Growing New Spinal Cells

Dan Fabulich (daniel.fabulich@yale.edu)
Thu, 3 Jun 1999 19:00:06 -0400 (EDT)

Growing New Spinal Cells
by Kristen Philipkoski

3:00 a.m. 3.Jun.99.PDT
Spinal cord researchers have accomplished what was previously thought impossible: tricking central nervous system cells into regeneration.

The inability of central nervous system cells to regenerate has been one of the most religiously defended dogmas in neurobiology. But Massachusetts General Hospital and Harvard University researchers have shown that by damaging the sciatic nerve -- the main sensory nerve to the leg -- they can activate growth signals in cells in the central nervous systems of laboratory rats.

If scientists can learn how to turn on growth signals without peripheral nerve injury, researchers may finally achieve what was once seen as an unreachable goal: the reconnection of a severed spinal cord.

In mammals, severed nerve fibers in the central branch of the spinal cord do not regenerate on their own. On the other hand, damaged peripheral nerves -- those that go to the extremities -- can heal themselves. Since the two branches, called axons, both make up the same neuron, researchers have been trying for decades to figure out why the cells behave so differently.

The difference in healing could be due to the cells not receiving the signals that kick-start growth in the nerve or to inhibitors in the cells preventing growth. Or possibly it's the result of an injury site, which frequently develops obstacles like cysts or holes in which cells can't grow.

"Our data looked at what happens if you can switch the cells into a growing
mode. The central branch, which never normally grows at all, began to grow right across the central spinal cord," said study leader Clifford Woolf, of the Neural Plasticity Research Group at the Massachusetts General Hospital Department of Anesthesia and Critical Care and the Harvard Medical School.

The research, published in the May issue of the scientific journal Neuron, showed cell growth into the spinal cord and above the injury site. If the sciatic nerve and central nervous system injuries happened at the same time, cells grew into the nervous system lesion, but not above it. But the researchers found that if they injured the sciatic nerve one to two weeks prior to the nervous system injury, cells grew into the spinal cord above the lesion.

"I think it's no longer an issue of science fiction. The current technology
to identify molecules in vivo should provide new treatments, we hope within a decade," Woolf said. "By then I think we will have made the scientific breakthrough necessary to plan therapy."

Wise Young, professor and director of the W.M. Keck Center for Collaborative Neuroscience at Rutgers University, believes that the research could lead to therapy that combines the many treatments in the works in laboratories today.

Combining cell-transfer treatments, which use fetal cells or stem cells to fill in holes, with growth mode treatments could yield dramatic results, said Young. Anti-inhibitor drugs, which are in clinical trials now, could also play a part in a combined treatment.

"We've seen some functional recovery, but we've not taken all the methods
and put them together into one combination therapy. If you build a bridge across the injury, it still won't grow all the way across because of inhibitors." Young said.

Actor Christopher Reeve's focus on spinal cord research has helped to advance research. Even conservative scientists are saying that they're hopeful for successful treatments in their lifetime. But according to experts, the funds necessary to provide therapies to people still fall short.

The total investment in spinal cord research in the United States from both private and government sources is less than US$100 million a year, Young estimated. In comparison, the pharmaceutical industry estimates that it costs an average of $300 million to take a single drug through clinical trials and into market.

Despite the limited resources, researchers remain encouraged.

"If you had asked any neuroscientist 10 years ago whether or not we would
see a spinal cord therapy, 99 percent would have said no, not in our lifetime, if at all," said Young. "By 1995 most scientists were saying it could possibly happen. In 1999, the majority are saying it not only can happen, but it will happen soon."

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